Self-propelled supramolecular nanomotors with temperature- responsive speed regulation Citation for published version (APA): Tu, Y., Peng, F., Sui, X., Men, Y., White, P. B., van Hest, J. C. M., & Wilson, D. A. (2017). Self-propelled supramolecular nanomotors with temperature-responsive speed regulation. Nature Chemistry, 9(5), 480-486. https://doi.org/10.1038/nchem.2674 DOI: 10.1038/nchem.2674 Document status and date: Published: 09/05/2017 Document Version: Accepted manuscript including changes made at the peer-review stage Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. 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If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, please follow below link for the End User Agreement: www.tue.nl/taverne Take down policy If you believe that this document breaches copyright please contact us at: [email protected] providing details and we will investigate your claim. Download date: 01. Oct. 2021 Self-propelled Supramolecular Nanomotors with Temperature-Responsive Speed Regulation This work has been published in: Tu, Y.; Peng, F.; Sui, X.; Men, Y.; White, P. B.; van Hest, J. C. M.; Wilson, D. A. Self-propelled supramolecular nanomotors with temperature-responsive speed regulation. Nat. Chem. 2016, doi:10.1038/nchem.2674 Abstract Self-propelled catalytic micro- and nanomotors have been the subject of intense study over the past few years, but it remains a continuing challenge to build in an effective speed-regulation mechanism. Movement of these motors is generally fully dependent on the concentration of accessible fuel, with propulsive movement only ceasing when the fuel consumption is complete. In this chapter we report a demonstration of control over the movement of self-assembled stomatocyte nanomotors via a molecularly built, stimulus-responsive regulatory mechanism. A temperature-sensitive polymer brush is chemically grown onto the nanomotor, whereby the opening of the stomatocytes is enlarged or narrowed on temperature change, which thus controls the access of hydrogen peroxide fuel and, in turn, regulates movement. To the best of our knowledge, this represents the first nanosized chemically driven motor for which motion can be reversibly controlled by a thermally responsive valve/brake. We envision that such artificial responsive nanosystems could have potential applications in controllable cargo transportation. 1 Introduction Recent advances in artificial micro- and nanomotors1-3 have brought their potential applications in the biomedical sciences closer4-9. Starting from the first centimeter-scale motors10, micro- and nano-tubular engines11-14, wires15,16, helices17,18, rods19-21, Janus motors22-24 and self-assembled polymeric motors8,25-27 scientists used both top-down or bottom-up approaches to design motors with high speeds and improved efficiency. These classes of motors can convert chemical fuel (such as hydrogen peroxide21,28-30, hydrazine31, acid32,33, water34, glucose27,35 and urea24) or external energy such as magnetic fields17,36,37, ultrasound19,38, electricity39,40, light41-43 or even organisms44 into mechanical motion45. Recently, new avenues to control the directionality of the nanomotors by mimicking taxis behavior inspired by nature were shown. These types of systems are however still based on external factors for the directional control of motion such as the presence of a gradient8. One of the limitations of current micro- and nanomotor systems is therefore still the limited control over their speed46-49. Some level of manipulation of the movement of micron-sized motors was previously achieved either by disassembling the whole micromotor under a thermal stimulus47 or by chemically inhibiting the catalytic enzymatic system49. The latter required sequential steps of inhibition and reactivation via addition of chemicals followed by multiple washings, which is not very practical for biomedical applications. Motor systems would be more versatile if equipped with a molecularly built stimuli-responsive valve or brake50, thus controlling and regulating the motion under the stimuli without changing the shape or assembly of the motor itself or by affecting its catalytic activity. Such property is particularly desirable for applications in the biomedical field and nanorobotics. In our previous work, we demonstrated the formation of self-assembled nanomotors, based on bowl-shaped polymer vesicles, known as stomatocytes, in which catalytic platinum nanoparticles were entrapped25. The narrow opening of the bowl shape structures serves as an outlet for the oxygen generated during the catalytic decomposition of the hydrogen peroxide fuel. Hydrogen peroxide is found naturally in the human body, especially in diseased areas such as tumor tissue and sites of inflammation. According to the literature51, human tumor cell lines can produce hydrogen peroxide at rates of up to 0.5 nmol/104 cells/h which is significant when related to the size of the tumor. Therefore nanomotor systems running on low concentrations of hydrogen peroxide with further ability to sense changes in the environment and regulate their speed and behavior via a stimuli-responsive valve or brake would be very attractive for biomedical applications. In this chapter we demonstrate the first nanomotor system with complete control over its speed by chemically attaching a stimulus-responsive valve system (polymer brush) to our engine that allows control of the motion of the nanovesicles without changing the catalyst activity or shape of the motor (Fig. 1). This doesn’t require the addition of chemicals into the system but instead the nanomotor is able to probe the environment and change its behavior by sensing the change in the outside temperature. Stimulus-responsive polymer brushes52 made of surface-tethered macromolecules are commonly known and have been widely applied in many areas, including the biomedical field53-55. Changes in the external environment (e.g., temperature, pH, light or redox states) can generally trigger a sharp and large response in the structure and properties of these grafted polymer layers56. Various polymer brushes have been synthesized via the SI-ATRP approach on different substrates using surface-attached initiators57, which allows accurate control of the structure and properties of the polymer brushes. By functionalizing the surface of the stomatocytes with a poly(N-isopropyl acrylamide) (PNIPAM) polymer brush via SI-ATRP a temperature-responsive polymer layer is introduced. Due to PNIPAM’s well-known LCST behavior58, increasing the temperature above its transition temperature leads to the collapse of the brushes, producing a hydrophobic layer on top of the small opening of the stomatocytes (less than 5 nm); this closes the aperture and prevents easy access of the fuel (hydrogen peroxide) inside the nanomotor (Fig. 1c, d). Due to the lack of fuel, the propelling movement of the motor will cease. The long molecularly built brushes function as a reversible brake system onto the nanomotors by controlling and regulating the access of the fuel inside the catalytic bowl shape structures with temperature. As the LCST behavior is reversible, by adjusting the temperature, the collapse of the PNIPAM brushes can be switched on and off, functioning thus as a regulatory mechanism to control the speed of the nanomotor (Fig. 1). This is in our view an elegant example of a brake system that doesn’t affect the catalytic activity or the shape of the motor but only its motion. It is also the closest mimic of a brake as found in automated cars from the macroscopic world. Figure 1 | Fabrication of polymeric stomatocyte nanomotors with thermo-sensitive brakes. a, Chemical structure of block copolymer PEG-b-PS and functionalized polymer Br-PEG-b-PS used for stomatocyte assembly. The polymers were synthesized via ATRP of styrene starting from a PEG macroinitiator. b, Schematic representation of the formation of PtNPs-loaded stomatocytes with ATRP initiator (PtNPs-Stoma-Br) and the subsequent growth of PNIPAM brushes by SI-ATRP on the surface of the stomatocytes. Polymersomes are formed by the self- assembly of PEG-b-PS and Br-PEG-b-PS in organic solvent. PtNPs were added subsequently and then entrapped during the shape transformation to form PtNPs-Stoma-Br. PtNPs-Stoma- Brush were obtained